During the coming year, we plan to complete an ongoing study of the "active metabolite" hypothesis. We are screening a large number of potential subjects using two tests for drug-metabolizing (hydroxylation) capacity, the phenylbutazone and antipyrine half-times. Subjects will be chosen from the extremes of these disapearance rates, so as to get contrasting samples of rapid and slow hydroxylators. A test dose of THC will be given intravenously. The clinical responses and the urinary metabolites will be studied. Our assumption is that if the active metabolite hypothesis is correct, rapid hydroxylators should have an earlier onset of clinical effects, a more intense peak, and a shorter duration of clinical effects than do the slow hydroxylators. We are also in the process of developing a "set" questionnaire for determining in advance the expectation of subjects in regard to marihuana effects, as this seems to be a major component of the variable responses among different subjects. We hope to be able to make more positive identification of some of the new metabolites we have isolated, but this will be largely contingent upon an expanding number of standard preparations and availability of GLC-MS equipment.